Unusual Autosomal Dominant Inheritance of Oculocutaneous Albinism Type 4 (OCA‐4): Clinical and Functional Features From A Chinese Family.

Oculocutaneous albinism (OCA) is a complex genetic disorder characterized by reduced or absent pigmentation in the skin, hair, and eyes. Among the eight known subtypes, OCA‐4 is caused by a mutation in SLC45A2, which plays a crucial role in melanin biosynthesis. While autosomal recessive inheritance is the most common pattern for all OCA subtypes, autosomal dominant cases are extremely rare. We report three patients from a Chinese family exhibiting autosomal dominant OCA‐4. Clinical assessments evaluated pigmentation and ocular features in affected family members. Next‐generation sequencing was performed to identify pathogenic variants, and functional studies in MNT‐1 cells were performed to explore the variant's biological effects. Patients exhibited mild hypopigmentation and foveal hypoplasia, consistent with the OCA‐4 phenotype. Genetic analysis identified a heterozygous c.208T>C (p.Tyr70His) variant in SLC45A2, the same variant that has been previously reported in association with autosomal dominant OCA‐4. Functional studies demonstrated that this variant caused protein retention in the endoplasmic reticulum, resulting in reduced melanin production. This family represents the first documented cases of autosomal dominant OCA‐4 in the Chinese population and only the second reported worldwide. Our findings confirm that the p.Tyr70His variant causes autosomal dominant OCA‐4. This study deepens our understanding of OCA‐4's genetic mechanisms and increases the complexity of its inheritance patterns in genetic counseling. [ABSTRACT FROM AUTHOR]